Th2 cytokines interleukin (IL)-4, 5, 9, 10 and granulocyte macrophage-colony stimulating factor, and the Th1/2 cytokine IL-3 have been importantly implicated as characterizing the immune responses in pathological allergic conditions. The differentiation, recruitment and activation of T cells, eosinophils and mast cells that produce or are regulated by these cytokines represent central components of these responses. Here, we define a previously unappreciated role for the mucosal integrin alphaEbeta7 in Th2 biased immunological responses. This integrin in predominantly expressed on mucosal T cells and can be induced on mast cells and certain dendritic cells, but is otherwise not expressed in the animal. We recently developed an alphaE deficient mouse that, together with blocking anti-alphaE specific monoclonal antibodies, have revealed an important role for this integrin in Th2 biased mucosal immune responses. Preliminary studies revealed that alphaE deficient (alphaE-/-) mice developed less pulmonary inflammation and airway hyperactivity after aerosolized ovalbumin exposure than wildtype (alphaE+/+) mice. Thus, in Aim 1, this finding will be confirmed in alphaE+/+ and alphaE-/- mice on an inbred genetic background and in alphaE+/+ mice after treatment with an ani-alphaEbeta7 monoclonal antibody, and will be extended to compare lymphocyte localization and phenotype. In Aim 2, T lymphocyte cytokine production by selected T cell subsets will be compared after aerosolized ovalbumin exposure in alphaE-/- and alphaE+/+ mice, and adoptive transfer experiments will be performed to define T cell subpopulations that can reconstitute the pulmonary response in alphaE-/- mice. These studies will reveal the role of alphaEbeta7 in this Th2 T cell/eosinophil based inflammation. The mast cell component of the allergic response is not readily studied in the pulmonary inflammation model. Thus, using a helminth infection model that induced T cell dependent reactive mast cell hyperplasia, we found the response to be augmented in alphaE deficient mice. In Aim 3, Trichinella spiralis induced mast cell hyperplasia will be compared in alphaE-/- and alphaE+/+ mice on an inbred genetic background, and in alphaE+/+ mice after treatment with anti-alphaEbeta7 antibodies. These studies are expected to confirm the important role of alphaEbeta7, and the cells that express it, in reactive mast cell hyperplasia. In addition, the impact of alphaE deficiency on T. spiralis induced mast cell progenitor recruitment, mucosal mast cell migration/differentiation, or resolution will be defined. In Aim 4, a mechanism will be sought for the enhanced reactive mast cell hyperplasia through the comparative study of T. spiralis induced changes in T cell localization and cytokine production, and adoptive transfer studies will be performed to determine whether it is alphaE deficiency on the T cells or the mast cells or both that results in augmented T. spiralis induced reactive mast cell hyperplasia.